Association between Dopamine Receptor D2 (DRD2) Variations rs6277 and rs1800497 and Cognitive Performance According to Risk Type for Psychosis: A Nested Case Control Study in a Finnish Population Sample.

Bottom Line:
Principal components factor analysis supported a three-factor model for cognitive measures.The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis.The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049).

Background: There is limited research regarding the association between genes and cognitive intermediate phenotypes in those at risk for psychotic disorders.

Methods: We measured the association between established psychosis risk variants in dopamine D2 receptor (DRD2) and cognitive performance in individuals at age 23 years and explored if associations between cognition and these variants differed according to the presence of familial or clinical risk for psychosis. The subjects of the Oulu Brain and Mind Study were drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986). Using linear regression, we compared the associations between cognitive performance and two candidate DRD2 polymorphisms (rs6277 and rs1800497) between subjects having familial (n=61) and clinical (n=45) risk for psychosis and a random sample of participating NFBC 1986 controls (n=74). Cognitive performance was evaluated using a comprehensive battery of tests at follow-up.

Results: Principal components factor analysis supported a three-factor model for cognitive measures. The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis. The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049).

Conclusion: The effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ according to the type (familial or clinical) risk for psychosis.

Mentions:
Principal components factor analysis of cognitive performance showed three eigenvalues >1, suggesting a three factor neurocognitive model (presented in Scree plot in Fig 1). These three factors accounted for 64% of performance variance. The loadings of the ten cognitive tests to the three factors are presented in Table 1. Broadly, WAIS vocabulary and verbal working memory (the digit span tasks) loaded best to factor 1 with some contribution from verbal fluency. We therefore termed this factor “verbal performance”. The pegboard tasks loaded best to factor 2, with a weaker loading also from verbal fluency. We termed this factor “psychomotor performance”. Matrix reasoning, PAL and SOC loaded best to factor 3, with weaker loading from logical memory. We termed this factor “non-verbal performance”.

Association between Dopamine Receptor D2 (DRD2) Variations rs6277 and rs1800497 and Cognitive Performance According to Risk Type for Psychosis: A Nested Case Control Study in a Finnish Population Sample.

Mentions:
Principal components factor analysis of cognitive performance showed three eigenvalues >1, suggesting a three factor neurocognitive model (presented in Scree plot in Fig 1). These three factors accounted for 64% of performance variance. The loadings of the ten cognitive tests to the three factors are presented in Table 1. Broadly, WAIS vocabulary and verbal working memory (the digit span tasks) loaded best to factor 1 with some contribution from verbal fluency. We therefore termed this factor “verbal performance”. The pegboard tasks loaded best to factor 2, with a weaker loading also from verbal fluency. We termed this factor “psychomotor performance”. Matrix reasoning, PAL and SOC loaded best to factor 3, with weaker loading from logical memory. We termed this factor “non-verbal performance”.

Bottom Line:
Principal components factor analysis supported a three-factor model for cognitive measures.The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis.The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049).

Background: There is limited research regarding the association between genes and cognitive intermediate phenotypes in those at risk for psychotic disorders.

Methods: We measured the association between established psychosis risk variants in dopamine D2 receptor (DRD2) and cognitive performance in individuals at age 23 years and explored if associations between cognition and these variants differed according to the presence of familial or clinical risk for psychosis. The subjects of the Oulu Brain and Mind Study were drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986). Using linear regression, we compared the associations between cognitive performance and two candidate DRD2 polymorphisms (rs6277 and rs1800497) between subjects having familial (n=61) and clinical (n=45) risk for psychosis and a random sample of participating NFBC 1986 controls (n=74). Cognitive performance was evaluated using a comprehensive battery of tests at follow-up.

Results: Principal components factor analysis supported a three-factor model for cognitive measures. The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis. The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049).

Conclusion: The effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ according to the type (familial or clinical) risk for psychosis.